HIV Susceptibility and Pathogenesis in the Female Genital Tract is designed to study mechanisms of HIV infection that are unique to women. Its four investigator initiated projects are strongly interactive and focus on HIV in the female genital tract. Project I, Microscopic Analysis of the Interaction of HIV and the Human Female Genital Tract (Thomas Hope, PhD, NWU), studies HIV interaction with tissue and mucous in the female genital tract. Project II, HIV and Female Genital Tract Flora (Greg Spear, PhD, RUMC), studies the effect of bacterial infection in the genital tract on susceptibility to HIV infection. Project III, HIV-Specific Immunity in Highly Exposed Uninfected Women (Richard Novak, MD, UIC and Linda Baum, PhD, RUMC), studies the potential development of protective mucosal immunity that results from sexual exposure to HIV. Project IV, Role of Estrogen in HIV Transmission and Pathogenesis (Lena AI-Harthi, PhD, RUMC), studies the effects of estrogen mediated leukocyte activation and Wnt/p-catenin signaling on HIV transmission. Four cores foster the collaborative interactions between projects. Core A (Administrative Core) is directed by the Program Project PI, Alan Landay, PhD, RUMC. Core B (Clinical Core) directed by Audrey French, MD, Cook County, will provide samples from established cohorts of HIV infected women: the Women's Interagency HIV Study (WIHS), the Women at Heterosexual Risk Cohort (WISH) and HIV infected women from Rwanda (RWISA). When necessary, women of interest from these established cohorts will be recruited to provide additional samples. Core C (Tissue Culture and Virology Laboratory Core) directed by Nell Lurain, PhD, RUMC, will perform experiments with the HIV tissue explant replication model, prepare molecular and virologic reagents, and maintain a specimen repository. Core D (Biostatistics/Epidemiology Core) directed by Elizabeth Golub, PhD, JHU, will help project investigators plan studies and evaluate results. The synergy of effort among projects and cores is evident in aims that require participation of multiple investigators and resources provided by the cores. This PO1 will improve our understanding of factors that enhance or inhibit sexual transmission of HIV and will lead to the development of innovative interventions to prevent HIV.